The Next Big Thing?

This post is from Guest Blogger, Stanley Nelson, M.D. Dr. Nelson is the Director for the UCLA Site of the NIH Neuroscience Microarray Consortium, and Professor of Human Genetics and Psychiatry at the David Geffen School of Medicine at UCLA. Dr. Nelson was also a co-author on last week’s collaborative Nature paper.

Investments in the genetics of autism have been substantial and the results are beginning to come forth, with last week’s announcement of the latest findings from our collaborative Autism Genome Project adding to previously identified genes and copy number variations that made last year’s Top 10 Autism Research Achievements of 2009. The latest results, funded in large part by the tremendous efforts of Autism Speaks, are interesting alone, and I hope that all have learned that there are indeed novel genes being identified that lead to autism. However, there is a perhaps more important message from the paper which relates directly to the couple hundred thousand families directly affected by an autism spectrum disorder in the US alone.

Within the recent Nature paper are compelling new findings demonstrating that autism can be caused by genetic mutations in a wide range of different genes, but the findings highlight how complex the genetic causes will be, likely in the hundreds. With this level of complexity, it is also clear that this sized sample that took 15-20 years to collect at the cost of tens of millions of dollars including molecular testing and analytical effort, we were only able to find genetic causes for a small minority of the children with autism (a few percent). So detecting the meaningful gene variants is largely a game of statistics. With the relatively small size of the autism samples available to us today, many gene mutations that may be causative in an individual with autism will go ‘undetected’ because our sample size lacks the statistical power to identify them as definitively associated with autism. This is because these causative variants are each “rare” in the whole autism population. Even though rare, each gene variant that confers risk is important. Why? When considered together, these gene variants will collectively explain the majority of cases of the disorder, as well as inform us greatly about the still largely unresolved biological causes, both genetic and environmental. To get us to the next phase of understanding the genetic risk of autism, we need a way to cost-effectively recruit tens of thousands of affected individuals and their families to enable the appropriate large scale genetic studies needed to address this pressing scientific need. My attitude is well described in an interview written by Nancy Shute at US News and World Report.

Until recently, we have not had a nationwide infrastructure that could allow anyone in the US to participate with a child with a diagnosis of autism. That has changed with the initiation of the IAN Genetics Project, funded byAutism Speaks through the High Risk, High Impact Initiative. Using the web portal of the IAN Genetics Project, families provide information about their child through simple web-based questionnaires that require only a few hours effort from home, anytime. Families also give consent for the DNA collection portion of study online. Interested families may participate in this study by taking their child to one of 1,600 blood draw sites nationwide with our corporate partner, Labcorp. This is all made possible through the Interactive Autism Network, and more information can be found at IANPROJECT.ORG, where I encourage all families with an affected child to register and complete the requested questionnaires. For those interested in learning more about the DNA Study, specific information can be found by following this link. Any questions about the project can be answered by IAN staff, who can be reached through the link.

Please register at IANPROJECT.ORG, even if not interested in the DNA Study. Simply filling out the online forms provides powerful new data to researchers that can only come from many thousands of individual families taking the time to help solve the complex issues of autism beyond genetics alone. Together we can take this next step to help reveal the causes of autism and help alleviate the struggles of those living with autism today.

We can analyze individual children or children with parents. Both are effective for the search for rare mutations that lead to autism. Parental DNA samples are useful for determining if the DNA mutation is inherited or a new mutation, and of course is useful clinically once the mutations are established to be truly associated with autism.

dugmaze

June 20, 2010 at 8:33 pm

Thanks Stan.
Another question. I read a post from a woman who claimed she took her son to get his DNA checked and they didn’t find anything although his father was autistic. I realize we don’t know where she went to get tested but is this possible? Wouldn’t the father’s DNA show up in the son’s DNA even if the son didn’t have autism?

Buy this beautiful ribbon and help support autism awareness.
I started making these for a friend and I donate $2 from each sale to The Autism Society. It’s my way of helping. Will you help me, help them.

i would like to find out what made my oldest different from my asd child.my oldest daughter is gifted and the asd child is only a few steps behind her in giftedness;i feel the need to find out what made them different.i would like to find out why my affected child has recooperated enough to be called adhd with austic traits and people tell me that austism is no longher associated with her person.

I applaud these efforts but this project is insanely expensive, time consuming and isn’t giving us sufficient value back on our investment. Meanwhile hundreds of treatment intervention studies go unfunded and environmental research, although emphasized with words, has received little action in terms of money and support of innovative science. We need to focus our very limited financial resources towards uncovering the environmental mechanisms causing the de novo mutations. There could easily be 50 variants of autism, this project could take 25 years- by that time autism could be affecting 1 in 50 boys. Naturally autism requires a genetic suseptibility – then what? What is turning on these rare gene variants that were dormat a generation ago.??? Our genes have barely changed in the past 25 yrs yet autism has increased 1,000%. Probably 95% of people w/ autism ( not aspergers) do not reproduce. If autism were primarily genetic autism would be rapidly decreasing!

It is certainly a fair point to state that the results may not justify the costs. The whole study ‘explains’ about 3% of why individual kids have autism. However, the cost of such projects should be rapidly decreasing as the cost for collecting genomic DNA samples and effectively (but minimally) phenotyping affected kids through IANPROJECT.ORG, with funding provided through Autism Speaks, we are now in a position to rapidly increase the sample size for genetic analysis in a cost effective manner. Collecting the sample has dominated the costs of these studies to date. If we do not identify the genetic causes, there is little hope for identifying the core basis of autism’s many forms, including how environmental insults contribute which will likely be in the context of specific mutations in many children (but of course not always). I would like to clarify that it is unlikely that environmental factors are playing a large role in causing these mutations. Mutations happen as part of our DNA passage from parents to kids, and there is no large increase in CNVs in autism kids than the control kids from the available data. And there are many rare genetic diseases that are clearly caused by spontaneous DNA mutations and are not caused by any environmental factor. We should expect autism spectrum disorders to be similar. The mutations that happened in the kids with autism are affecting genes that have a role in brain development, a small number of which are now observed to be clearly contributing to autism risk. Very rare mutations (maybe occurring in only one in one thousand kids) appear to be the rule. Thus, we will learn about the mutations that happened in the set of kids whose DNA is studied, and these DNA findings will be the basis of our understanding of autism. So it is best to have as many different affected people as possible to participate in the DNA studies. There are likely hundreds of variants of autism and all deserve to be identified so that a larger portion of parents have a discrete known cause for their child.

I respectfully disagree w/ you assertion that it is unlikely the environment plays a role in the mutation and I think you will find that 90% parents of children under 10 agree w/me. What we are seeing now is a different type of autism than the one geneticists have been studying for 20 yrs. Yes, there are many rare genetic diseases like Retts and Huntingtons in which a normally progressing person suddenly lurches backwards into a terrible and sometimes fatal regression. These are all single gene diseases and have little in common with autism in terms of autism vast hetereogenity. There are also NOT diseases growing at an astonishing rate.

It is a given in the autism community that the environment plays a very strong in the explosion of autism cases. I hope you talk to Geri Dawson and get her opinion. That said I am talking specifically about children like my own who were where healthy, speaking, affectionate, athletic toddlers who regressed into a state of catatonia, chronic illnesses, severe rashes, horrible life ruining allergies, seizures, inflammatory bowel disease- NONE of which are found in our family. The difference w/ my son’s autism and the autism you are studying is his autism manifested itself after 4 days of fever following 7 vaccines in one day. He has never been the same. My son was not programmed to self destruct.

He deserves answers as well as the parents of clearly genetically driven autism.

Katie, I’m so sorry to hear what you’ve been through. Look, there is NO doubt SOME kids with autistic features or full blown autism acquired autism by being damaged in some way, to vaccines. Most likely, they were allergic to the ingredients or hypersensitive to the side effects. Frankly, I’m tired of all the research, because while millions goes to people sitting in labs playing with rats and looking at brains, thousands of parents are sitting at home going crazy because they have LITTLE help to handle the day to day operations of living with autism. We need more research into the brain function of our politicians, as to determine why such callous indifference to such a incredible challenge and national threat to our population. No doubt as well, we live in a toxic world. God only knows what’s in our food and water that can’t be helping our brains. Especially autistic brains, already compromised and in need of healing and improvement. I say skip the autism research and start funneling the money into researchig how to set up nursing or caregiving centers so parents dealing with severe autism can get a damn break. You tube has some good videos about severe autism. Too bad the researchers wouldn’t check out your son and others who are featured on you tube, to see if they could help. I mean think about it. So what if they discover what causes autism, which they won’t of course, ever, because it’s become too big of an industry….and it’s rooted in multiple etiologies….so as usual, we will be TEASED every few months with a potential “new exciting discovery” that will never be anything concrete or helpful to those currently living with real autism.